Vaccination strategies for mitigation of MERS-CoV outbreaks
Authors: Mohammad Bosaeed, Naif Khalaf Alharbi
Journal: The Lancet Global Health (2023)

MERS-CoV infections have been reported over the past 10 years in 27 countries, with most cases occurring in Saudi Arabia (84%) and with a high case fatality rate. In 2022, sporadic cases of Middle East respiratory syndrome (MERS) were still being reported in the eastern Mediterranean region.1WHOMERS situation update.https://applications.emro.who.int/docs/WHOEMCSR630E-eng.pdf?ua=1Date: December 2022Date accessed: February 27, 2023Google Scholar Dromedary camels (Camelus dromedarius) serve as an animal reservoir from which infection can spill over into humans.2Mackay IM Arden KE MERS coronavirus: diagnostics, epidemiology and transmission.Virol J. 2015; 12: 222Crossref PubMed Scopus (249) Google Scholar, 3Aljasim TA Almasoud A Aljami HA et al.High rate of circulating MERS-CoV in dromedary camels at slaughterhouses in Riyadh, 2019.Viruses. 2020; 121215Crossref PubMed Scopus (10) Google Scholar Efforts to develop an effective and safe human MERS-CoV vaccine have progressed, with a few vaccine candidates having reached human studies; these vaccines are based on DNA platforms (GLS-5300)4Modjarrad K Roberts CC Mills KT et al.Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial.Lancet Infect Dis. 2019; 19: 1013-1022Summary Full Text Full Text PDF PubMed Scopus (203) Google Scholar and viral vector platforms (ChAdOx15Bosaeed M Balkhy HH Almaziad S et al.Safety and immunogenicity of ChAdOx1 MERS vaccine candidate in healthy Middle Eastern adults (MERS002): an open-label, non-randomised, dose-escalation, phase 1b trial.Lancet Microbe. 2022; 3: e11-e20Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar and modified vaccinia Ankara [MVA])6Koch T Dahlke C Fathi A et al.Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial.Lancet Infect Dis. 2020; 20: 827-838Summary Full Text Full Text PDF PubMed Scopus (98) Google Scholar incorporating the MERS-CoV spike antigen. In The Lancet Global Health, a mathematical modelling study by Daniel Laydon and colleagues7Laydon DJ Cauchemez S Hinsley WR Bhatt S Ferguson NM Impact of proactive and reactive vaccination strategies for health-care workers against MERS-CoV: a mathematical modelling study.Lancet Glob Health. 2023; 11: e759-e769Summary Full Text Full Text PDF Scopus (1) Google Scholar provides support for the importance of having an efficient preparedness plan for future MERS-CoV outbreaks. The study considers a wide range of important factors, closing knowledge gaps related to vaccination strategies for emerging pathogens such as MERS-CoV. Based on this study's quantitative and data-driven foundation, an effective MERS-CoV vaccine could substantially decrease the morbidity and mortality of MERS. Policy makers could implement diverse strategies to approach future outbreaks, using vaccination as an effective and impactful measure; such a strategy could be as simple as reactively vaccinating health-care workers at high risk of MERS-CoV infection during outbreaks, which could be very cost-effective. The study mathematically modelled the effect of a MERS-CoV vaccine for health-care workers in averting cases when multiple factors are considered: vaccine efficacy, duration of vaccine protection, time to outbreak (in proactive vaccination strategy), time to response (in a reactive vaccination strategy), and animal reservoir control measures. Although the study did not model what factors would constitute reservoir control or what the range of its effect would be, it shows that reservoir control measures alone could have a major role in reducing the number of cases. These control measures seem to be a key complementary factor to a proactive vaccination strategy, even with a vaccine efficacy of more than 75%. Ideally, and per the model, a long duration of vaccine protection and high vaccine efficacy are required in order to prevent a high percentage of cases in a proactive vaccination strategy. By contrast, the study showed that reactive vaccination—in response to a hospital outbreak—outperforms proactive vaccination. This approach is not affected by vaccine efficacy or duration of protection. The more rapid (<30 days) reaction could avert 50% of cases when vaccine efficacy is 75%.7Laydon DJ Cauchemez S Hinsley WR Bhatt S Ferguson NM Impact of proactive and reactive vaccination strategies for health-care workers against MERS-CoV: a mathematical modelling study.Lancet Glob Health. 2023; 11: e759-e769Summary Full Text Full Text PDF Scopus (1) Google Scholar The model considered a duration of vaccine protection of 1–20 years; however, platforms used for developing MERS-CoV vaccines, such as the ChAdOx1 platform, have shown short durations of immunogenicity and protection when used against SARS-CoV-2.8Voysey M Clemens SAC Madhi SA et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.Lancet. 2021; 397: 99-111Summary Full Text Full Text PDF PubMed Scopus (3001) Google Scholar The DNA platform has never been approved for use in humans, despite tremendous clinical trials.9Hill AV Reyes-Sandoval A O'Hara G et al.Prime-boost vectored malaria vaccines: progress and prospects.Hum Vaccin. 2010; 6: 78-83Crossref PubMed Scopus (179) Google Scholar MVA has been approved as a whole inactivated virus vaccine for smallpox and mpox (formerly known as monkeypox), and has also been approved as a recombinant vector vaccine.10Volkmann A Williamson A-L Weidenthaler H et al.The Brighton Collaboration standardized template for collection of key information for risk/benefit assessment of a modified vaccinia Ankara (MVA) vaccine platform.Vaccine. 2021; 39: 3067-3080Crossref PubMed Scopus (20) Google Scholar Given the capability of the current platforms and use of the spike antigen, similar to SARS-CoV-2 vaccines, the upper end of the protection duration range used in the model is reasonably unlikely: durations of only 6 months to 1 year might apply. Laydon and colleagues' study7Laydon DJ Cauchemez S Hinsley WR Bhatt S Ferguson NM Impact of proactive and reactive vaccination strategies for health-care workers against MERS-CoV: a mathematical modelling study.Lancet Glob Health. 2023; 11: e759-e769Summary Full Text Full Text PDF Scopus (1) Google Scholar used data from the 2013–14 outbreak in Saudi Arabia, which represented an unexpected invasion of a novel viral illness, when infection control measures in the country were not as effective as they are now; however, findings based on this scenario might be applicable to other inexperienced hospitals or countries. The magnitude of the next MERS-CoV outbreak might not involve nosocomial transmission, which could affect the model's findings. Additionally, the model was based on the assumption that vaccine efficacy would not be affected by genetic variations in MERS-CoV; although the spike protein used in most vaccine candidates seems relatively stable, it is important to characterise vaccines against all available MERS-CoV strains or variants. Due to the low prevalence of MERS-CoV infections, it is not feasible to evaluate vaccine efficacy and the duration of seroprotective immune responses in clinical trials; however, innovative approaches could be sought using animal models and larger phase 2 trials to prepare stockpiles for emergency use, whereas phase 3 efficacy could be evaluated during outbreaks. Laydon and colleagues' study7Laydon DJ Cauchemez S Hinsley WR Bhatt S Ferguson NM Impact of proactive and reactive vaccination strategies for health-care workers against MERS-CoV: a mathematical modelling study.Lancet Glob Health. 2023; 11: e759-e769Summary Full Text Full Text PDF Scopus (1) Google Scholar used high-quality methods and advanced analyses, and answers central questions regarding a MERS-CoV vaccination policy and preparedness for the next epidemic. Current MERS-CoV vaccine candidates have been shown to be safe and elicit antibody and T-cell immune responses. However, no studies have investigated the potential population-level impact of MERS-CoV vaccination. While this viral infection is still circulating in camels and is reported sporadically in humans, Laydon and colleagues' study7Laydon DJ Cauchemez S Hinsley WR Bhatt S Ferguson NM Impact of proactive and reactive vaccination strategies for health-care workers against MERS-CoV: a mathematical modelling study.Lancet Glob Health. 2023; 11: e759-e769Summary Full Text Full Text PDF Scopus (1) Google Scholar is crucial in continuing the unfinished work of developing a safe and effective MERS-CoV vaccine. Experience in the rapid development of COVID-19 vaccines provides practical guidance for producing effective and safe MERS-CoV vaccines. It is essential to focus on the possibility of future outbreaks and to have a preparedness plan that considers these models in vaccination strategies. Affected countries should have plans for maintaining MERS-CoV vaccine stockpiles that are sufficiently available and ready to use, especially in populations at high risk of infection during outbreaks. We declare no competing interests. Impact of proactive and reactive vaccination strategies for health-care workers against MERS-CoV: a mathematical modelling studySubstantial reduction of MERS-CoV morbidity and mortality is possible when vaccinating only health-care workers, underlining the need for countries at risk of outbreaks to stockpile vaccines when available. Full-Text PDF Open Access